Recent studies have suggested that use of depot medroxyprogesterone acetate (DMPA) may have an adverse effect on bone mineral density (BMD). In contrast, use of oral contraceptives has been reported to have a beneficial effect or no effect. In a preliminary study, we observed a decrease of 3.0 percent in BMD among users of DMPA as compared with an increase of 0.1 percent-2.9 percent among users of 30-35 mug pills. Questions regarding the specific relationship between BMD and DMPA, however, have not been fully addressed. Furthermore, almost no data are available on the effects of the recently marketed pills containing only 20 mug of estradiol. Considering that over 11 million women in the US use hormonal contraception each year, it seems imperative to obtain accurate information on the effects of these medications on skeletal health. To address this important question, we propose to conduct a prospective clinical trial comparing changes in BMD over a 2-year interval experienced by women using DMPA or oral contraceptives containing 20 mug estradiol as compared with women not using hormonal contraception. Each cohort will be comprised of 229 women aged 16 to 33 years of white, black, or Hispanic race/ethnicity. The primary outcomes (ie, BMD and biomarkers of bone metabolism) will be analyzed to assess changes from baseline within each contraceptive group at 6, 12, 18, and 24 months as compared to changes observed among controls. Furthermore, we will be able to assess the reversibility of potential adverse effects of hormonal contraception on BMD among those who discontinue their method by conducting a bone scan and measuring biomarkers at the point of discontinuation and at 6-month intervals from this point. This study will be among the first to investigate the role of race/ethnicity and age in contraceptive-related BMD changes while accounting for behavioral correlates (eg, prior contraceptive use, nutritional intake, exercise habits, alcohol use, smoking) in a multivariate fashion. Ultimately, this study will determine which women, if any, are placed at increased risk of osteopenia or osteoporosis as a result of using these hormonal contraceptives during their reproductive years.